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[show abstract]
[hide abstract]
ABSTRACT: Infanrix hexa™, a diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated poliomyelitis, and Haemophilus influenzae type b (Hib) conjugate vaccine, is indicated for primary and booster vaccination of infants. Available clinical data from more than a decade of experience with the vaccine indicate that primary and booster vaccination with Infanrix hexa™ is a safe and useful option for providing protection against the common childhood diseases of diphtheria, tetanus, poliomyelitis, pertussis, hepatitis B, and disease caused by Hib.
Paediatric Drugs 08/2012; 14(5):337-43. · 1.79 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: Prophylaxis or on-demand therapy with octocog alfa, antihemophilic factor, plasma/albumin-free method (Advate(®)) is effective for the prevention and treatment of bleeding episodes and for perioperative management in pediatric and adult patients with hemophilia A. Routine prophylaxis with Advate(®) also prevents bleeding episodes in patients with hemophilia A; moreover, routine prophylaxis with Advate(®) is more effective in preventing bleeding episodes than on-demand therapy. Advate(®) is generally well tolerated in patients with hemophilia A. Serious adverse events with Advate(®) therapy include the development of high-titer factor VIII inhibitors (usually in previously untreated patients) and hypersensitivity reactions. There are no comparative trials of Advate(®) and other factor VIII concentrates. Nevertheless, current evidence indicates that Advate(®) is an effective option for the management of pediatric and adult patients with hemophilia A.
BioDrugs 08/2012; 26(4):269-73. · 3.44 Impact Factor
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Sohita Dhillon
[show abstract]
[hide abstract]
ABSTRACT: Aripiprazole (Abilify®) is an atypical antipsychotic indicated for the treatment of mania associated with bipolar I disorder. It is unique in its class, as it is a partial agonist of dopamine D(2) and D(3), and serotonin 5-HT(1A) receptors and a modest antagonist of 5-HT(2A) receptors. This article reviews the pharmacological properties, clinical efficacy and tolerability of oral aripiprazole in the management of mania associated with bipolar I disorder in adults. In well designed clinical trials in patients with recent manic or mixed episodes associated with bipolar I disorder, oral aripiprazole monotherapy or adjunctive therapy to lithium or valproate improved symptoms of mania following short-term (≤12 weeks) or maintenance (≤100 weeks) treatment. In addition, maintenance treatment with aripiprazole (as monotherapy or adjunctive therapy) prevented the recurrence of any mood episodes or manic episodes (but not depressive episodes) in patients who had previously been stabilized and maintained on aripiprazole. Aripiprazole was generally well tolerated in these studies and was associated with a low risk of prolactin elevation, corrected QT interval prolongation and metabolic disturbances. Extrapyramidal symptoms occurred in up to 28% of aripiprazole recipients, but after longer-term treatment (≤100 weeks), symptom severity did not differ significantly from that in placebo recipients. Aripiprazole treatment generally did not increase bodyweight to a clinically relevant extent; however, more patients receiving aripiprazole monotherapy than placebo had clinically significant bodyweight gain during 100 weeks' treatment. Additionally, in a comparative trial, aripiprazole monotherapy was at least as effective as haloperidol monotherapy in terms of improving symptoms of mania, but had the advantage of a lower incidence of some adverse events, such as extrapyramidal symptom-related adverse events. Further trials comparing aripiprazole with other agents, including atypical antipsychotics, would help to definitively position aripiprazole relative to these agents. Current guidelines recommend aripiprazole as a first-line option (as monotherapy or adjunctive therapy) for the short-term treatment of mania associated with bipolar I disorder, and as a first-line (as monotherapy) or second-line (as adjunctive therapy) option for preventing the recurrence of mood episodes during longer-term therapy.
Drugs 01/2012; 72(1):133-62. · 4.23 Impact Factor
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Sohita Dhillon
[show abstract]
[hide abstract]
ABSTRACT: Tesamorelin (Egrifta™) is a synthetic analog of human growth hormone-releasing hormone (also known as growth hormone-releasing factor) that stimulates the synthesis and release of endogenous growth hormone. It is the first and, so far, only treatment indicated for the reduction of excess abdominal fat in patients with HIV-associated lipodystrophy. This article reviews the pharmacological properties, clinical efficacy and tolerability of tesamorelin in patients with HIV-associated central fat accumulation. Subcutaneous tesamorelin was effective in reducing visceral adipose tissue (VAT), but did not affect subcutaneous adipose tissue to a clinically significant extent in two 26-week, well designed, clinical trials in patients with HIV-associated central fat accumulation. This reduction in VAT was maintained in the longer term in patients who continued to receive tesamorelin until week 52 in the extension phases of the two trials. However, discontinuation of therapy during this period resulted in the reaccumulation of VAT. Tesamorelin therapy was also associated with significant improvements in other body composition measures (e.g. trunk fat and waist circumference) and improvements were generally seen in some body image parameters (e.g. belly image distress). Tesamorelin was generally well tolerated, with treatment-emergent serious adverse events occurring in <4% of patients during 26 weeks of therapy. Most of these events were injection-site reactions or events known to be associated with growth hormone therapy (e.g. arthralgia, headache and peripheral edema). Although long-term clinical experience is needed to further assess the benefits and risks of therapy, current evidence suggests that tesamorelin may be useful for reducing visceral adiposity in patients with HIV-associated lipodystrophy, thereby potentially improving self image.
BioDrugs 12/2011; 25(6):405-8. · 3.44 Impact Factor
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ABSTRACT: Bevacizumab (Avastin™) is a humanized monoclonal antibody directed against vascular endothelial growth factor. In patients with human epidermal growth factor receptor type 2 (HER2)-negative metastatic breast cancer, bevacizumab is indicated as first-line therapy in combination with paclitaxel, or in combination with capecitabine when treatment with other chemotherapy options, including taxanes or anthracyclines, is not considered appropriate. This article reviews the efficacy and tolerability of these combination therapies in the first-line treatment of patients with metastatic breast cancer, and summarizes the pharmacological properties of bevacizumab. In randomized, controlled, phase III trials in patients with predominantly HER2-negative metastatic or locally recurrent breast cancer, the addition of bevacizumab to paclitaxel or capecitabine significantly prolonged progression-free survival (PFS; investigator assessment) by a median of 5.9 and 2.9 months, respectively, relative to paclitaxel or capecitabine alone. It also significantly increased the objective response rate, but not overall survival. Independent reviews of data supported the results of the primary analyses of investigator-assessed PFS. However, as the efficacy of bevacizumab in combination with capecitabine appears to be less than that of other available options, it should be used only if treatment with other chemotherapy options are not considered appropriate. The addition of bevacizumab to paclitaxel had no significant adverse effects on health-related quality of life. Efficacy data from two routine clinical practice studies were generally consistent with those from the phase III trials. Bevacizumab had generally acceptable tolerability when administered in combination with paclitaxel or capecitabine as first-line therapy in these studies, and adverse events were consistent with the known tolerability profiles of the individual agents. The most common adverse events associated with bevacizumab combination therapy in phase III trials were sensory neuropathy and grade ≥3 hypertension, occurring more frequently with combination therapy than with chemotherapy alone. Potentially life-threatening events, such as venous thromboembolism, gastrointestinal perforation, arterial thromboembolism, haemorrhage and left ventricular dysfunction, occurred in ≤5% of patients receiving combination therapy in these trials. In conclusion, bevacizumab administered in combination with paclitaxel, or in combination with capecitabine if other chemotherapy regimens are not appropriate, may be considered as an option for the first-line treatment of patients with HER2-negative metastatic breast cancer.
Drugs 11/2011; 71(16):2213-29. · 4.23 Impact Factor
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Sohita Dhillon
[show abstract]
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ABSTRACT: Rivastigmine, a cholinesterase inhibitor, is available as a transdermal patch (Exelon® patch, Rivastach® patch, Prometax® patch) for the treatment of mild to moderate Alzheimer's disease. Rivastigmine transdermal patch was effective, in terms of improving cognitive and global function, and generally well tolerated in patients with mild to moderate dementia of the Alzheimer's type in a large, well designed trial. Most adverse events associated with rivastigmine patch were mild to moderate in severity, with the patch generally better tolerated than oral rivastigmine, especially in terms of cholinergic gastrointestinal adverse events. The patch also had good skin adhesion and a favourable skin tolerability profile in this study, with most application-site reactions being mild in severity. Additionally, in a safety and tolerability study, rivastigmine patch, regardless of concomitant memantine therapy, was generally well tolerated in patients switching from oral donepezil therapy. Thus, current evidence suggests that rivastigmine transdermal patch is an effective treatment option for patients with Alzheimer's disease, with the potential for improving compliance and providing sustained clinical benefit because of its ease of use and generally favourable tolerability profile.
Drugs & Aging 11/2011; 28(11):927-30. · 2.67 Impact Factor
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Sohita Dhillon
[show abstract]
[hide abstract]
ABSTRACT: Evicel® is a fibrin sealant consisting of two components, human clottable protein (predominantly human fibrinogen) and human thrombin. It is indicated as supportive treatment in patients undergoing surgery when control of bleeding by standard surgical techniques is ineffective or impractical. Evicel® is a new formulation of the previously available fibrin sealant Quixil® (in the EU) or Crosseal™ (in the US). Evicel® differs from Quixil®/Crosseal™ in that its fibrinogen component does not contain the antifibrinolytic agent tranexamic acid, which is potentially neurotoxic, resulting in Quixil®/Crosseal™ being contraindicated for use in neurosurgery. The removal of tranexamic acid did not affect the haemostatic efficacy or longevity of Evicel® fibrin clots and allowed the sealant to be granted an expanded indication. Evicel® and Quixil®/Crosseal™ are easy to use and, since they do not contain synthetic or bovine aprotinin, have a reduced potential for hypersensitivity reactions. This article reviews the pharmacological properties, clinical efficacy and tolerability of Evicel® and its previous formulation as supportive treatment for haemostasis in surgery. In clinical studies, Evicel® and Quixil®/Crosseal™ were generally well tolerated and effective haemostatic agents for adjunctive use in various types of surgeries when conventional methods were impractical or ineffective in controlling bleeding. Two pivotal, randomized studies showed that Evicel® was significantly more effective than manual compression in patients undergoing vascular surgery, and significantly more effective than Surgicel® in patients undergoing retroperitoneal or intra-abdominal surgery, as assessed by the proportion of patients achieving haemostasis. In another similarly designed pivotal study in patients undergoing liver resection, Crosseal™ was significantly more effective than standard haemostatic agents (e.g. Surgicel®), as assessed by the mean time to haemostasis. The incidences of treatment-emergent adverse events in these studies were generally similar between the Evicel® or Crosseal™ groups and the comparator groups. Quixil® was also generally well tolerated and an effective haemostatic agent in endonasal surgeries, and tonsillectomies and/or adenoidectomies, with some benefit of treatment with Evicel® or Quixil® also observed in orthopaedic surgeries. Although additional comparative studies with other haemostatic agents would help to definitively position Evicel® with respect to these agents, current evidence suggests that Evicel® is useful in surgeries for improving haemostasis where standard surgical techniques are insufficient.
Drugs 10/2011; 71(14):1893-915. · 4.23 Impact Factor
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Sohita Dhillon
[show abstract]
[hide abstract]
ABSTRACT: Rivastigmine, a cholinesterase inhibitor, is available as a transdermal patch (Exelon(®) patch, Rivastach(®) patch, Prometax(®) patch) for the treatment of mild to moderate Alzheimer's disease. Rivastigmine transdermal patch was effective, in terms of improving cognitive and global function, and generally well tolerated in patients with mild to moderate dementia of the Alzheimer's type in a large, well designed trial. Most adverse events associated with rivastigmine patch were mild to moderate in severity, with the patch generally better tolerated than oral rivastigmine, especially in terms of cholinergic gastrointestinal adverse events. The patch also had good skin adhesion and a favourable skin tolerability profile in this study, with most application-site reactions being mild in severity. Additionally, in a safety and tolerability study, rivastigmine patch, regardless of concomitant memantine therapy, was generally well tolerated in patients switching from oral donepezil therapy. Thus, current evidence suggests that rivastigmine transdermal patch is an effective treatment option for patients with Alzheimer's disease, with the potential for improving compliance and providing sustained clinical benefit because of its ease of use and generally favourable tolerability profile.
Drugs 06/2011; 71(9):1209-31. · 4.23 Impact Factor
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[show abstract]
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ABSTRACT: Erlotinib is a low molecular weight, orally active, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. Inhibition of EGFR tyrosine kinase results in the disruption of processes involved in cancer growth and development, including cell migration, proliferation, angiogenesis, and apoptosis. In the well designed, phase III SATURN study, oral erlotinib 150 mg/day as maintenance treatment prolonged progression-free survival (PFS) in patients with non-small-cell lung cancer (NSCLC) who had not progressed after four cycles of first-line platinum doublet chemotherapy. PFS was significantly longer with erlotinib than with placebo in patients who were analyzable for PFS and in the subgroup of these patients with EGFR immunohistochemistry-positive tumors (co-primary endpoints). The improvement in PFS was independent of several baseline and clinical characteristics, including histology, smoking status, and EGFR mutation status, although a greater treatment benefit was observed in patients with tumors bearing EGFR-activating mutations than in those with wild-type EGFR tumors. Overall survival in the SATURN study was significantly longer with erlotinib than with placebo in the intent-to-treat population, in patients with EGFR immunohistochemistry-positive tumors, and in patients with wild-type EGFR tumors. Median overall survival had not yet been reached in patients with tumors bearing EGFR-activating mutations. Oral erlotinib as maintenance therapy was generally well tolerated in patients with NSCLC in the SATURN study and had a tolerability profile generally similar to that observed in a trial of erlotinib monotherapy as second-line treatment in patients with NSCLC.
BioDrugs 06/2011; 25(3):139-46. · 3.44 Impact Factor
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Sohita Dhillon
[show abstract]
[hide abstract]
ABSTRACT: Tesamorelin (Egrifta™) is a synthetic analogue of human growth hormone-releasing hormone (also known as growth hormone-releasing factor) that stimulates the synthesis and release of endogenous growth hormone. It is the first and, so far, only treatment indicated for the reduction of excess abdominal fat in patients with HIV-associated lipodystrophy. This article reviews the pharmacological properties, clinical efficacy and tolerability of tesamorelin in patients with HIV-associated central fat accumulation. Subcutaneous tesamorelin was effective in reducing visceral adipose tissue (VAT), but did not affect subcutaneous adipose tissue to a clinically significant extent in two 26-week, well designed, clinical trials in patients with HIV-associated central fat accumulation. This reduction in VAT was maintained in the longer term in patients who continued to receive tesamorelin until week 52 in the extension phases of the two trials. However, discontinuation of therapy during this period resulted in the reaccumulation of VAT. Tesamorelin therapy was also associated with significant improvements in other body composition measures (e.g. trunk fat and waist circumference) and improvements were generally seen in some body image parameters (e.g. belly image distress). Tesamorelin was generally well tolerated, with treatment-emergent serious adverse events occurring in <4% of patients during 26 weeks of therapy. Most of these events were injection-site reactions or events known to be associated with growth hormone therapy (e.g. arthralgia, headache and peripheral oedema). Although long-term clinical experience is needed to further assess the benefits and risks of therapy, current evidence suggests that tesamorelin may be useful for reducing visceral adiposity in patients with HIV-associated lipodystrophy, thereby potentially improving self image.
Drugs 05/2011; 71(8):1071-91. · 4.23 Impact Factor
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Sohita Dhillon
[show abstract]
[hide abstract]
ABSTRACT: Naproxen/esomeprazole is a fixed-dose combination of the NSAID naproxen and the proton pump inhibitor esomeprazole. In two well designed, 12-week studies, naproxen/esomeprazole fixed-dose combination was noninferior to celecoxib in treating the signs and symptoms of disease in patients with osteoarthritis of the knee, as assessed by the mean change from baseline in Western Ontario and McMaster Universities Osteoarthritis Index pain and function scores and Patient Global Assessment scores (coprimary endpoints). Two other studies showed that the cumulative incidence of gastric ulcers (primary efficacy measure) was significantly lower with naproxen/esomeprazole than with enteric-coated naproxen alone during up to 6 months' therapy in patients with osteoarthritis, rheumatoid arthritis, ankylosing spondylitis or any other condition requiring daily NSAID therapy. The fixed-dose combination was generally well tolerated in these studies, with an upper gastrointestinal tolerability profile generally better than that of naproxen and similar to that of celecoxib.
Drugs & Aging 03/2011; 28(3):237-48. · 2.67 Impact Factor
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Sohita Dhillon
[show abstract]
[hide abstract]
ABSTRACT: Infanrix hexa, administered intramuscularly, is a diphtheria, tetanus, acellular pertussis, hepatitis B (HBV), inactivated poliomyelitis and Haemophilus influenzae type b (Hib) conjugate vaccine, indicated for primary and booster vaccination of infants. Infanrix hexa should be administered as a two- or three-dose primary vaccination course in infants aged < or =6 months, followed by booster vaccination between 11 and 18 months of age, with an interval of at least 6 months between the last dose of primary vaccination and the booster dose. This spotlight reviews the immunogenicity and protective effectiveness, as well as the reactogenicity and safety of Infanrix hexa. Infanrix hexa as primary and booster vaccination was safe and highly immunogenic for all its component toxoids/antigens in infants aged <2 years, regardless of vaccination schedules. Its immunogenicity and safety profiles were generally similar to those of currently available vaccines, the diphtheria, tetanus and acellular pertussis-based pentavalent vaccines plus monovalent HBV or Hib vaccines. In large clinical studies, Infanrix hexa elicited a strong immune response against vaccine toxoids/antigens, as indicated by high seroprotection/seropositivity/vaccine response rates and geometric mean titers. Moreover, antibodies against vaccine toxoids/antigens persisted for up to a mean of approximately 6 years after booster vaccination, and the vaccine induced long-term immune memory against hepatitis B surface antigen and Hib antigen. A strong immune response against Infanrix hexa toxoids/antigens after primary vaccination was also induced in infants who had received a dose of HBV vaccine at birth and in pre-term infants, although the response in the latter group was somewhat lower than that in full-term infants. In addition, when coadministered with other childhood vaccines, the immunogenicity of Infanrix hexa or that of the concomitantly administered vaccine was generally not altered. Hexavalent vaccines, including Infanrix hexa, were protective against invasive Hib disease; Infanrix hexa is also expected to be protective against pertussis. Most solicited local and general symptoms with Infanrix hexa were mild to moderate in intensity and the vaccine was associated with few unsolicited adverse events. Available clinical data from more than 10 years' experience with the vaccine suggest that Infanrix hexa as primary and booster vaccination is a safe and useful option for providing protection against the common childhood diseases of diphtheria, tetanus, poliomyelitis, pertussis, hepatitis B and invasive Hib disease.
BioDrugs 10/2010; 24(5):299-302. · 3.44 Impact Factor
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ABSTRACT: This is a review of the pharmacology of strontium ranelate (Protelos, Protos, Protaxos, Bivalos, Osseor), and its efficacy and tolerability in the treatment of patients with postmenopausal osteoporosis. Strontium ranelate is a divalent strontium salt of ranelic acid that is capable of increasing bone formation and reducing bone resorption, thereby uncoupling and rebalancing bone turnover in favour of bone formation. The drug is effective in reducing the risk of fractures, including both vertebral and nonvertebral fractures, in patients with postmenopausal osteoporosis, according to data from two large, double-blind, placebo-controlled, multicentre trials of 5 years' duration, and reduced the risk of hip fracture in high-risk patients in a post hoc analysis of one trial. Moreover, data from patients who continued to receive the drug during the 3-year extension phase of these trials indicate that strontium ranelate continues to provide protection against new vertebral fractures and nonvertebral fractures for up to 8 years of therapy. It also improves bone mineral density at numerous sites and both increases markers of bone formation and decreases markers of bone resorption. Strontium ranelate is administered orally as a suspension and is generally well tolerated. The nature of adverse events was generally similar regardless of treatment duration in clinical trials, with the most commonly reported being nausea and diarrhoea over 5 years of treatment, and memory loss and diarrhoea during longer-term treatment. Although an increased risk of venous thromboembolism was associated with strontium ranelate relative to placebo over 5 years of treatment in a pooled analysis of clinical trials, postmarketing data have not confirmed this finding. Overall, the clinical data available suggest that strontium ranelate is an effective and generally well tolerated option for the first-line treatment of postmenopausal osteoporosis.
Drugs & Aging 09/2010; 27(9):771-3. · 2.67 Impact Factor
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Sohita Dhillon
[show abstract]
[hide abstract]
ABSTRACT: Infanrix hexa, administered intramuscularly, is a diphtheria, tetanus, acellular pertussis, hepatitis B (HBV), inactivated poliomyelitis and Haemophilus influenzae type b (Hib) conjugate vaccine, indicated for primary and booster vaccination of infants. Infanrix hexa should be administered as a two- or three-dose primary vaccination course in infants aged <or=6 months, followed by booster vaccination between 11 and 18 months of age, with an interval of at least 6 months between the last dose of primary vaccination and the booster dose. This article reviews the immunogenicity and protective effectiveness, as well as the reactogenicity and safety of Infanrix hexa. Infanrix hexa as primary and booster vaccination was safe and highly immunogenic for all its component toxoids/antigens in infants aged <2 years, regardless of vaccination schedules. Its immunogenicity and safety profiles were generally similar to those of currently available vaccines, the diphtheria, tetanus and acellular pertussis-based pentavalent vaccines plus monovalent HBV or Hib vaccines. In large clinical studies, Infanrix hexa elicited a strong immune response against vaccine toxoids/antigens, as indicated by high seroprotection/seropositivity/vaccine response rates and geometric mean titres. Moreover, antibodies against vaccine toxoids/antigens persisted for up to a mean of approximately 6 years after booster vaccination, and the vaccine induced long-term immune memory against hepatitis B surface antigen and Hib antigen. A strong immune response against Infanrix hexa toxoids/antigens after primary vaccination was also induced in infants who had received a dose of HBV vaccine at birth and in pre-term infants, although the response in the latter group was somewhat lower than that in full-term infants. In addition, when coadministered with other childhood vaccines, the immunogenicity of Infanrix hexa or that of the concomitantly administered vaccine was generally not altered. Hexavalent vaccines, including Infanrix hexa, were protective against invasive Hib disease; Infanrix hexa is also expected to be protective against pertussis. Most solicited local and general symptoms with Infanrix hexa were mild to moderate in intensity and the vaccine was associated with few unsolicited adverse events. Available clinical data from more than 10 years' experience with the vaccine suggest that Infanrix hexa as primary and booster vaccination is a safe and useful option for providing protection against the common childhood diseases of diphtheria, tetanus, poliomyelitis, pertussis, hepatitis B and invasive Hib disease.
Drugs 05/2010; 70(8):1021-58. · 4.23 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: This is a review of the pharmacology of strontium ranelate (Protelos, Protos, Protaxos, Bivalos, Osseor), and its efficacy and tolerability in the treatment of patients with postmenopausal osteoporosis. Strontium ranelate is a divalent strontium salt of ranelic acid that is capable of increasing bone formation and reducing bone resorption, thereby uncoupling and rebalancing bone turnover in favour of bone formation. The drug is effective in reducing the risk of fractures, including both vertebral and nonvertebral fractures, in patients with postmenopausal osteoporosis, according to data from two large, double-blind, placebo-controlled, multicentre trials of 5 years' duration, and reduced the risk of hip fracture in high-risk patients in a post hoc analysis of one trial. Moreover, data from patients who continued to receive the drug during the 3-year extension phases of these trials indicate that strontium ranelate continues to provide protection against new vertebral fractures and nonvertebral fractures for up to 8 years of therapy. It also improves bone mineral density at numerous sites and both increases markers of bone formation and decreases markers of bone resorption. Strontium ranelate is administered orally as a suspension and is generally well tolerated. The nature of adverse events was generally similar regardless of treatment duration in clinical trials, with the most commonly reported being nausea and diarrhoea over 5 years of treatment, and memory loss and diarrhoea during longer-term treatment. Although an increased risk of venous thromboembolism was associated with strontium ranelate relative to placebo over 5 years of treatment in a pooled analysis of clinical trials, postmarketing data have not confirmed this finding. Overall, the clinical data available suggest that strontium ranelate is an effective and generally well tolerated option for the first-line treatment of postmenopausal osteoporosis.
Drugs 04/2010; 70(6):733-59. · 4.23 Impact Factor
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Sohita Dhillon
[show abstract]
[hide abstract]
ABSTRACT: Sitagliptin (Januvia, Glactiv(R), Tesavel(R)) is a dipeptidyl peptidase-4 inhibitor indicated for the treatment of type 2 diabetes mellitus. Oral sitagliptin as monotherapy or combination therapy was generally well tolerated and improved glycaemic control in well designed clinical trials in patients with type 2 diabetes. Glycosylated haemoglobin (HbA(1c)) levels were significantly reduced with sitagliptin monotherapy relative to voglibose monotherapy or placebo, and with sitagliptin as initial combination therapy with metformin or pioglitazone relative to monotherapy with these agents or placebo. Moreover, sitagliptin monotherapy was noninferior to metformin monotherapy in terms of the reduction in HbA(1c) levels. Significant reductions in HbA(1c) levels, relative to background therapy, were also observed with sitagliptin add-on therapy to ongoing treatment with thiazolidinediones, sulfonylureas or insulin with or without metformin, or metformin alone. In terms of the reduction in HbA(1c) levels as add-on treatment to metformin, sitagliptin was noninferior to glipizide and generally did not differ from rosiglitazone, and as add-on treatment to pioglitazone, it did not differ significantly from metformin. Sitagliptin had a low risk of hypoglycaemia (except when used in combination with agents that may be associated with hypoglycaemia, such as sulfonylureas or insulin) and was generally weight-neutral. Although additional comparative data and longer-term studies with glycaemic and clinical outcomes are required to definitively position sitagliptin relative to other antihyperglycaemic agents, current evidence suggests that it is a useful treatment option for patients with type 2 diabetes, with potential advantages including oral administration, a generally weight-neutral effect and a low risk of hypoglycaemia.
Drugs 03/2010; 70(4):489-512. · 4.23 Impact Factor
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Sohita Dhillon
[show abstract]
[hide abstract]
ABSTRACT: Tramadol/paracetamol 37.5 mg/325 mg (Tramacet, Zaldiar, Ixprim, Kolibri) is an orally administered fixed-dose combination of the atypical opioid tramadol and paracetamol, which is indicated in the EU for the symptomatic treatment of moderate to severe pain. This article reviews the pharmacological properties, clinical efficacy and tolerability of tramadol/paracetamol in adults with moderate to severe pain. Fixed-dose tramadol/paracetamol is a rapidly-acting, longer-duration, multimodal analgesic, which is effective and generally well tolerated in patients with moderate to severe pain. In several well designed, clinical studies, single- or multiple-dose tramadol/paracetamol was effective in providing pain relief in adult patients with postoperative pain after minor surgery, musculoskeletal pain (acute, subacute or chronic), painful diabetic peripheral neuropathy or migraine pain. It was also effective as an add-on analgesic in patients who were experiencing moderate to severe musculoskeletal pain (e.g. osteoarthritis or rheumatoid arthritis pain) despite ongoing NSAID and/or disease-modifying antirheumatic drug therapy. Moreover, in patients with postoperative pain, ankle sprain pain or subacute lower back pain, the analgesic efficacy of tramadol/paracetamol was better than that of paracetamol, generally similar to, or better than that, of tramadol, and generally similar to that of ibuprofen or the fixed-dose combinations hydrocodone/paracetamol, codeine/paracetamol and codeine/paracetamol/ibuprofen. In addition, the analgesic efficacy of tramadol/paracetamol did not differ significantly from that of gabapentin in patients with chronic pain associated with diabetic peripheral neuropathy. Tramadol/paracetamol had no additional tolerability issues relative to its components and, overall, the tolerability profile of tramadol/paracetamol was generally similar to that of other active comparators (fixed-dose combinations or single-agents); however, incidences of some adverse events were lower in tramadol/paracetamol than in active comparator recipients. Although additional comparative and long-term studies would help to definitively position tramadol/paracetamol with respect to other analgesics, available clinical data suggest that tramadol/paracetamol is a useful treatment option for providing multimodal analgesia in patients with moderate to severe pain.
Clinical Drug Investigation 01/2010; 30(10):711-38. · 1.82 Impact Factor
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ABSTRACT: Atazanavir (Reyataz), a protease inhibitor (PI), is approved in many countries for use as a component of antiretroviral therapy (ART) regimens for the treatment of adult, and in some countries in paediatric, patients with HIV-1 infection. ART regimens containing ritonavir-boosted atazanavir improved virological and immunological markers in adult patients with HIV-1 infection, and had similar efficacy to regimens containing lopinavir/ritonavir in treatment-naive and treatment-experienced patients. In addition, unboosted atazanavir was noninferior to ritonavir-boosted atazanavir in treatment-naive patients. Atazanavir is administered once daily and has a low capsule burden. Atazanavir, whether unboosted or boosted, was generally well tolerated and appeared to be associated with less marked metabolic effects, including less alteration of lipid levels, than other PIs. These properties mean that boosted atazanavir, and unboosted atazanavir in patients unable to tolerate ritonavir, continues to have a role as a component of ART regimens in patients with HIV-1 infection.
Drugs 02/2009; 69(8):1107-40. · 4.23 Impact Factor
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ABSTRACT: Recombinant teriparatide (Forteo; Forsteo) is an anabolic (bone-forming) agent. Studies have shown that subcutaneous teriparatide 20 microg/day is effective in women with postmenopausal osteoporosis, men with idiopathic or hypogonadal osteoporosis, and patients with glucocorticoid-induced osteoporosis. Teriparatide improves bone mineral density (BMD) and alters the levels of bone formation and resorption markers; histomorphometric studies have shown teriparatide-induced effects on bone structure, strength, and quality. Subcutaneous teriparatide 20 microg/day administered over a treatment period of 11-21 months was effective in reducing the risk of fractures and improving BMD in men with idiopathic or hypogonadal osteoporosis, women with postmenopausal osteoporosis, and patients with glucocorticoid-induced osteoporosis. Furthermore, the beneficial effects of teriparatide on vertebral fracture prevention and BMD appear to persist following treatment cessation. Teriparatide is generally well tolerated and treatment compliance rates are favorable. However, current limitations on the length of treatment and the high acquisition cost mean that teriparatide is best reserved for the treatment of patients with osteoporosis at high risk of fracture, or for patients with osteoporosis who have unsatisfactory responses to or intolerance of other osteoporosis therapies.
BioDrugs 02/2009; 23(3):197-9. · 3.44 Impact Factor
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Sohita Dhillon
[show abstract]
[hide abstract]
ABSTRACT: Bosentan (Tracleer) is an orally administered dual endothelin-1 (ET-1) receptor antagonist approved in the EU for reducing the number of new digital ulcers in patients with systemic sclerosis and ongoing digital ulcer disease. Oral bosentan therapy was beneficial and generally well tolerated in patients with digital ulcers associated with systemic sclerosis. In well designed, placebo-controlled trials, bosentan treatment significantly reduced the number of new ulcers, but had no effect on ulcer healing, in patients with digital ulcers. Adverse events associated with bosentan were consistent with those seen during treatment for other indications, with major concerns being the potential for teratogenicity and hepatotoxicity, for which regular liver function monitoring is recommended. Overall, considering the large unmet need for therapeutic options in patients with digital ulcers, bosentan extends the treatment options available to patients with systemic sclerosis-associated digital ulcers.
Drugs 01/2009; 69(14):2005-24. · 4.23 Impact Factor
